肿瘤负荷缓解介导慢性肾脏病4期肾功能改善：白蛋白结合型紫杉醇联合环磷酰胺 + 曲妥珠单抗治疗HER2阳性乳腺癌一例报告

Improvement of Renal Function in Stage 4 Chronic Kidney Disease Mediated by Tumor Burden Reduction: A Case Report of HER2-Positive Breast Cancer Treated with Nab-Paclitaxel Combined with Cyclophosphamide and Trastuzumab

摘要: 目的：结合肿瘤肾脏病学理论与国内外临床研究，观察白蛋白结合型紫杉醇联合环磷酰胺、曲妥珠单抗用于病因未病理确诊的慢性肾脏病4期(CKD4期)HER2阳性乳腺癌患者的肾脏安全性，探讨肿瘤完全缓解是否存在介导重度肾损伤修复的潜在可能性。方法：回顾1例保乳术后64岁女性患者临床资料，患者合并高血压病、糖尿病，但患者拒绝肾穿刺活检，肾损伤病理病因无法明确。经乳腺外科、肾内科等MDT依据肾脏耐受情况个体化下调环磷酰胺剂量；并且全程规范控压，每周期充分水化、碱化尿液开展肾脏保护治疗。同时动态监测血肌酐、估算肾小球滤过率(eGFR)、尿微量白蛋白、尿白蛋白/肌酐比值(UACR)及水肿、泡沫尿等肾病症状，同步记录肿瘤疗效与各类不良事件。结果：患者完整完成辅助化疗、1年曲妥珠单抗维持治疗及乳腺放疗，肿瘤可达到临床完全缓解。基线eGFR47.8 mL/(min∙1.73m²)，伴血肌酐升高、大量微量白蛋白尿；抗肿瘤治疗后血肌酐持续下降，eGFR可升高，尿蛋白指标进行性降低，水肿、泡沫尿等症状可基本消退。全程无急性肾损伤、3级及以上肾毒性、心力衰竭、重度骨髓抑制等严重不良反应。曲妥珠单抗经网状内皮系统代谢，肾脏排泄极少；白蛋白结合型紫杉醇以胆道排泄为主；环磷酰胺经减量联合水化可降低肾小管损伤；肿瘤相关慢性炎症减轻、长期SGLT2抑制剂干预、规范化水化多重因素共同参与肾脏指标改善的过程。结论：多学科协作、个体化剂量调整联合全程护肾干预下，该三联方案可为病因不明CKD4期HER2阳性乳腺癌安全治疗提供案例证据。肿瘤负荷完全缓解提示存在减轻肾小球高滤过、改善滤过屏障、改善肾功能的潜在作用。本研究为单病例回顾观察，存在肾损伤病理不明、多重护肾与抗肿瘤混杂干预等固有局限，无法确立肿瘤缓解与肾功能改善的直接因果关系，相关结论仅具备临床启发价值，尚需大样本队列进一步验证。

Abstract: Objective: Combining the theory of onconephrology and domestic and foreign clinical studies, to observe the renal safety of nab-paclitaxel combined with cyclophosphamide and trastuzumab in HER2-positive breast cancer patients with stage 4 chronic kidney disease (CKD stage 4) of unknown etiology, and to explore the potential possibility that complete tumor remission may mediate the repair of severe renal injury. Methods: The clinical data of a 64-year-old female patient after breast-conserving surgery were retrospectively analyzed. The patient was complicated with hypertension and diabetes, but she refused renal biopsy, so the pathological etiology of renal injury could not be clarified. The MDT including breast surgery and nephrology departments individually reduced the cyclophosphamide dose according to renal tolerance; standardized blood pressure control was implemented throughout the treatment course, and adequate hydration and urine alkalization were performed in each cycle for renal protective therapy. Meanwhile, serum creatinine, estimated glomerular filtration rate (eGFR), urinary microalbumin, urinary albumin/creatinine ratio (UACR), and nephropathy symptoms such as edema and foamy urine were dynamically monitored, and tumor efficacy and all types of adverse events were recorded simultaneously. Results: The patient completed adjuvant chemotherapy, 1-year trastuzumab maintenance therapy and breast radiotherapy in full course, and the tumor achieved clinical complete remission. Baseline eGFR was 47.8 mL/(min·1.73 m²), accompanied by elevated serum creatinine and massive microalbuminuria; serum creatinine continuously decreased, eGFR increased, urinary protein indicators progressively declined, and symptoms including edema and foamy urine basically subsided after anti-tumor treatment. No serious adverse reactions such as acute kidney injury, grade 3 or higher renal toxicity, heart failure, severe myelosuppression occurred during the whole treatment process. Trastuzumab is metabolized via the reticuloendothelial system with minimal renal excretion; nab-paclitaxel is mainly excreted through the biliary tract; dose-reduced cyclophosphamide combined with hydration can avoid renal tubular injury; Alleviation of tumor-related chronic inflammation, long-term SGLT2 inhibitor intervention and standardized hydration jointly participated in the improvement of renal indicators. Conclusion: Under multidisciplinary collaboration, individualized dose adjustment and full-course renal protective intervention, this triple regimen can provide case evidence for safe treatment of HER2-positive breast cancer patients with undefined CKD stage 4. Complete remission of tumor suggests a potential effect on alleviating glomerular hyperfiltration, repairing filtration barrier and improving renal function. As a single-case retrospective observation, this study has inherent limitations including unknown renal pathology and multiple confounding renal-protective and anti-tumor interventions. Direct causal relationship between tumor remission and renal improvement cannot be established, and relevant conclusions are only clinically suggestive and need further verification by large cohorts.